This invention relates to apparatus and a method which enables improved use of artificial kidneys in hemodialysis. More particularly, it concerns an improved dialysate circuit for separating liquid from blood at a precise pre-selected rate and quantity during hemodialysis, and a method which uses the improved apparatus and controls transmembrane pressure by control of the rate of liquid removal from the circuit.
The apparatus includes a closed, controlled volume circuit which incorporates improvement means that insure maintenance of the hydraulic, or liquid, integrity of the circuit sufficiently accurately to enable pre-selection of the desired ultrafiltration rate and maintenance thereof without physician or technician change of operating parameters throughout the entire hemodialysis treatment. These improvement means include piston and cylinder units for supply of dialysate to and from the kidney that resemble heretofore known units but in the preferred embodiment a pair of such units are herein combined with a third piston and cylinder control unit in a new manner and arrangement which provides a new method of operation and control of the hemodialysis treatment relative to heretofore clincally employed methods. The new method, and apparatus, in reliance on the improved, precise hydralulic integrity of the dialysate circuit, uses the third piston and cylinder unit to positively withdraw from that circuit the exact amount of liquid, or ultrafiltrate, which is equal to the excess water desired to be removed from the renal insufficiency patient being treated. Due to the positive withdrawal demand by the third piston and cylinder unit, pressures within the sub-atmospheric pressure portion of the circuit and most importantly the pressure differential between the blood and dialysate sides of the kidney, i.e., the transmembrane pressure, changes as a function of that demand and pressure isolation elements maintain that pressure irrespective of blood pressure changes, or downstream pressure changes on the dialysate. The result is an automatic changing of pressure across the membrane to the pressure which is required to ultrafiltrate water from the blood at the preset rate demanded and controlled by the operation of piston and cylinder unit.
Otherwise stated, the new method intentionally causes the transmembrane pressure to float to the subatmospheric pressure which will supply an ultrafiltration rate demanded by the operator-set liquid removal rate. Such method of operation basically differs from the clincially used prior method in which the physician or technician selected the initial transmembrane pressure and thereafter attempted to maintain that set transmembrane pressure throughout the four to six hour hemodialysis treatment by making periodic alterations responsive to observed excursions from the pre-set transmembrane pressure. It also basically differs from methods which employ positive pressure on the blood to attain the desired transmembrane pressure.
A most important advantage which results from the use of the new method, and apparatus, of this invention is that it provides precise removal of the desired amount of excess water from the patient, at the rate best suited to the requirements of the individual patient, and maintains the rate of that removal substantially uniform on a continuous, automatic basis. This result is achieved irrespective of changes which may occur, and normally do occur in the impedence across the semi-permeable membrane or hollow fiber wall surfaces, to liquid separation from the blood due to clotting or other blocking of the minute openings in the membrane, or to uncontrollable changes which may occur in the pressure on the blood side of the artificial kidney, and is therefore more precise and reliable than clincially used procedures that rely on the assumption that the artificial kidney will maintain throughout the entire hemodialysis its designed, or new condition, K.sub.UF, i.e., its ability to pass water as a function of transmembrane pressure.
The method of this invention, and the apparatus to enable its performance, differs from all known prior devices and methods even though this area of hemodialysis treatment has received an extensive amount of attention and research in the past. A review of prior attempts to measure ultrafiltration rate and volume in hemodialysis is below set forth as background basis for identifying the differences which characterize this invention.
As above suggested, prior clinical practice has made use of measurements of ultrafiltrate during hemodialysis by making manual changes to the pressure on the dialysate side of the membrane during the hemodialysis after periodic observation of instantaneous measurements of the quantity or rate of ultrafiltrate being removed. After making the change to a pressure considered corrective by the technician or operator the apparatus maintains the newly selected transmembrane pressure until it is later reset, as necessary. U.S. Pat. No. 3,990,973 shows such a system; it describes an ultrafiltration measuring system which interrupts dialysate flow to and from the kidney and during the interruption measures the ultrafiltrate being generated. The dynamic transmembrane pressure in the artificial kidney at the instant of interruption is maintained during the period required to measure the ultrafiltrate in a rotameter. After comparing the measured rate with the initially set rate, the difference is used as a guide to the operator in resetting the transmembrane pressure to a value intended to achieve the initial ultrafiltrate removal objective for the hemodialysis treatment.
Other patents which disclose means for collecting ultrafiltrate in a graduated cylinder, or its equivalent, during hemodialysis and control the process by making manual changes in the operating parameters which determine transmembrane pressure include U.S. Pat. Nos. 3,669,880, 3,969,069, 3,979,284, 4,021,341 and 4,093,545. Certain of these patents employ a closed recirculation circuit which includes the artificial kidney and employ a pair of pumps, or piston-cylinder means, or cylinders provided with diaphragms for supplying equal quantities of dialysate to and from the kidney and withdraws a portion of the spent dialysate into a measuring vessel. For example, U.S. Pat. No. 4,021,341 shows a system in which input and output pumps are linked to provide substantially equal volumes of dialysate to and from an artificial kidney and dialysate output in excess of dialysate input is separated and measured to thereby monitor the instantaneous rate of ultrafiltration and total ultrafiltration volume. The rate is measured in a rotameter, and after observation is used by the operator as the basis for manually changing the input dialysate attenuator setting and/or the output dialysate pressure amplifier setting to thereby change the transmembrane pressure as needed to control ultrafiltration rate. This system includes the inaccuracies inherent in pump operation and matching of pumped volumes over a four to six hour hemodialysis treatment; it also has the disadvantage of permitting recirculation of spent dialysate to the kidney and this recirculation decreases dialysis efficiency, or requires frequent manual inspection to prevent pressure attenuator settings that allow such spent dialysate recirculation.
U.S. Pat. No. 4,093,545 shows a dialysate supply chamber which supplies dialysate to an artificial kidney and recieves spent dialysate and ultrafiltrate from the kidney and provides a visible measuring tube to indicate the ultrafiltrate additions in the level of the dialysate storage chamber.
The article entitled "Clinical Evaluation of a Pre-set Ultrafiltration Rate Controller Available for Single Pass and Hemodiafiltration Systems", Artificial Organs, May, 1978, pp. 141-143, discloses for a single pass system the provision of dialysate to and from an artificial kidney by employing twin chambers outfitted with vertically oriented diaphragms. Removal of a certain amount of the spent dialysate in the closed system is stated to cause negative pressure to develop on the dialysate side of the membrane and resultant ultrafiltration of water through the membrane. This system includes a degasser in the spent dialysate line to remove gas from the withdrawn dialysate prior to its measurement.
The article entitled "The Accurate Control of Ultrafiltration", Artificial Organs, pp. 144-146, May, 1978, describes a pair of isovolumetric pumps in the form of two pistons mounted on a common shaft which reciprocate in chambers provided with valves and a switching system similar to that disclosed in U.S. Pat. No. 3,406,826 to thereby supply dialysate to, and remove spent dialysate from, an artificial kidney in a closed dialysis circuit; this circuit employs a peristaltic pump adjacent to the kidney to remove a portion of the spent dialysate which is collected in a visible graduated cylinder.
The dialysate flow control systems commercially available from Fluid Metering Inc., Oyster Bay, N.Y., which are designated F2MX and F4M2 employ a pump in an efferent line from an artificial kidney to withdraw spent dialysate from a closed system; in one of the possible modes of operation using pairs of cylinders fitted with pistons, or diaphragms, to supply dialysate to the kidney the slaved relationship between the pistons or diaphragms, imposes an ultrafiltration demand on the membrane. These systems measure withdrawn spent dialysate after degassing only the withdrawn fluid.
The importance of removing gas from fluids removed from blood which are being used to monitor the progress of a hemodialysis treatment is recognized in U.S. Pat. No. 4,054,522; that patent further recognizes that a major source of error in attempts to monitor dialysate volumes, particularly in single pass systems, has been the inclusion of gases in the circulating dialysate and that patent proposes to degas liquids in the apparatus therein described which uses reciprocating diaphragms in chambers having different volumes.